Down's syndrome is one of the most frequent diseases relating to autosomal aberrations. A Down's syndrome patients has the chromosome No.21 in a somatic cell which is not a normal duplicate chromosome but is a trisomy (triplicate), which leads to a mental retardation, abnormal development, heart disease, leukemia, early Alzheimer's disease.
The results of many investigations made so far on the isolation, identification and functional analysis of the causative genes of this disease indicated that (1) the gene of Single-minded 2 (hereinafter designated as Sim2) known as a transcription regulatory factor playing an important role in the development and differentiation of a central nervous system cell is present in a critical region (q22.2) for the Down's syndrome on the human chromosome No.21, that (2) an increased Sim2 gene expression product in a cell is suggested to be a pathogenic component of the Down's syndrome since the Down's syndrome becomes symptomatic even when only this narrow critical region becomes trisomy, and that (3) a transcription inhibiting complex formed as a result of the binding between a transcription coupling factor classified into an ARNT family such as ARNT1 or ARNT2 (hereinafter sometimes referred to as an ARNT family transcription coupling factor) and a Sim2 exhibits an inhibitory action on a CME sequence (5′-ACGTG-3′: a core sequence of an element required for the transcription in the midline in the central nervous system, which is the nucleotide sequence of a DNA to which the protein complex of this transcription coupling factor with the Sim2 can be bound), and more typically, an investigation of the Sim2 function for the activity on the transcription of a reporter gene comprising a CME sequence-carrying promoter bound functionally thereto revealed that the Sim2 has a potent inhibitory effect even on the transcription activity of an ARNT family coupling factor which is an auxiliary factor as its binding partner (i.e., transcription coupling factor) and a Sim2/ARNT family transcription coupling factor heterodimer complex (i.e., a transcription inhibiting complex formed as a result of the binding between the ARNT family transcription coupling factor and the Sim2) was revealed to have an inhibitory effect on the CME sequence, and the promotion of the transcription inhibition by this transcription inhibiting complex is now considered to be one of the causes of the Down's syndrome.
Based on the findings discussed above, a transcription activating complex allowing a transcription regulatory factor/ARNT family transcription coupling factor heterodimer complex to exhibit a promotive activity on the CME sequence has been desired to be found and forced to act competitively against the Sim2/ARNT family transcription coupling factor heterodimer complex, whereby achieving an application to the treatment of the Down's syndrome.